Candidate (Dr. Michael Henry): I completed my residency in Psychiatry at the University of Massachusetts Medical Center, and my fellowship in Psychopharmacology at the National Institute of Mental Health (NIMH). Currently, I am Director of Electroconvulsive Therapy (ECT) at McLean Hospital. While at the NIMH, I was responsible for a positron emission tomography (PET) study of the effects of ECT on cerebral glucose metabolism (3). Since my arrival at McLean Hospital I have collaborated with Drs Perry Renshaw, Bruce Cohen, and others, using various magnetic resonance imaging techniques to study the effects of treatment interruption (4,19), the antidepressant effects of CDP-choline, and brain pharmacokinetics (5,20). My long-term objectives are to 1) understand the pathophysiology of depression using brain-imaging techniques; and 2) define the mechanisms by which treatments for depression exert their antidepressant effects. Environment: Bruce Cohen, M.D., Ph.D., the mentor for this proposal, is an internationally respected scientist and teacher, who will provide mentoring on research methods, study design, data analysis, and my overall development as an independent researcher. The didactic component of this proposal includes direct mentoring, tutorials, and consultation from experts at and outside McLean Hospital; course work in neuroanatomy, statistics, computers, and ethics at Harvard University and MIT; visiting fellowships to three other imaging laboratories; and direct hands-on research with the support of three additional MR physicists. The Brain Imaging Center (BIC) is well equipped to support this type of training. Under the direction of Perry Renshaw, M.D., Ph.D., has a reputation for excellence in both rapid sequence imaging techniques and magnetic resonance spectroscopy. The techniques to be used in this study have been utilized successfully in pilot studies described in the proposal. Research: The present study proposes to use dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) to define changes in regional cerebral blood volume (CBV) that occur when female patients, who have responded well to fluoxetine, relapse into depression following medication discontinuation.